P16INK4A EXPRESSION AS A POTENTIAL PROGNOSTIC MARKER IN CERVICAL PRECANCEROUS AND CANCEROUS LESIONS IN MOROCCO

Introduction :The overexpression of p16INK4a is considered to be strong and consistent in HPV-induced cancers. The objective of this study was to investigate the presence of HPV DNA in cervical biopsies, and to study the overexpression of p16INK4a as a marker of precancerous and cancerous lesions of the cervix. Material and methods :A total of 75 cervical biopsies were included in this study involving cervicitis (n = 11), mild dysplasia (n = 17), severe dysplasia (n = 30) and invasive carcinomas (n = 17). The presence of HPV was assessed using an examination in situ hybridization (CSA). p16INK4a protein expression was investigated by immunohistochemistry. Results: p16INK4a expression was very low in benign cervical lesions, while 18.8% of these lesions showed positivity for HPV DNA detection. Forty seven percent of mild dysplastic lesions presented overexpression of p16INK4a protein, and 76.4% were HPV positive. Strong signal of p16INK4a was observed in 100% of severe dysplastic lesions, and in 94.2% of invasive carcinoma. HPV DNA was detected in 83.3% of severe dysplastic lesions, and in 82.3% of invasive carcinoma. Conclusion: This pattern of overexpression demonstrates the potential use of p16INK4a as a diagnostic marker to recognize evolution of precancerous disease in the cervix

P16INK4A EXPRESSION AS A POTENTIAL PROGNOSTIC MARKER IN CERVICAL PRECANCEROUS AND CANCEROUS LESIONS IN MOROCCO

Introduction :The overexpression of p16INK4a is considered to be strong and consistent in HPV-induced cancers. The objective of this study was to investigate the presence of HPV DNA in cervical biopsies, and to study the overexpression of p16INK4a as a marker of precancerous and cancerous lesions of the cervix. Material and methods :A total of 75 cervical biopsies were included in this study involving cervicitis (n = 11), mild dysplasia (n = 17), severe dysplasia (n = 30) and invasive carcinomas (n = 17). The presence of HPV was assessed using an examination in situ hybridization (CSA). p16INK4a protein expression was investigated by immunohistochemistry. Results: p16INK4a expression was very low in benign cervical lesions, while 18.8% of these lesions showed positivity for HPV DNA detection. Forty seven percent of mild dysplastic lesions presented overexpression of p16INK4a protein, and 76.4% were HPV positive. Strong signal of p16INK4a was observed in 100% of severe dysplastic lesions, and in 94.2% of invasive carcinoma. HPV DNA was detected in 83.3% of severe dysplastic lesions, and in 82.3% of invasive carcinoma. Conclusion: This pattern of overexpression demonstrates the potential use of p16INK4a as a diagnostic marker to recognize evolution of precancerous disease in the cervix

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Nanostructured Na₂CaP₂O₇: A New and Efficient Catalyst for One-Pot Synthesis of 2-Amino-3-Cyanopyridine Derivatives and Evaluation of Their Antibacterial Activity

A facile and novel synthesis of thirteen 2-amino-3-cyanopyridine derivatives 5(a–m) by a one-pot multicomponent reactions (MCRs) is described for the first time, starting from aromatic aldehydes, malononitrile, methyl ketones, or cyclohexanone and ammonium acetate in the presence of the nanostructured diphosphate Na2CaP2O7 (DIPH) at 80 °C under solvent-free conditions. These compounds were brought into existence in a short period with good to outstanding yields (84–94%). The diphosphate Na2CaP2O7 was synthesized and characterized by different techniques (FT-IR, XRD, SEM, and TEM) and used as an efficient, environmentally friendly, easy-to-handle, harmless, secure, and reusable catalyst. Our study was strengthened by combining five new pyrido[2,3-d]pyrimidine derivatives 6(b, c, g, h, j) by intermolecular cyclization of 2-amino-3-cyanopyridines 5(b, c, g, h, j) with formamide. The synthesized products were characterized by FT-IR, 1H NMR, and 13C NMR and by comparing measured melting points with known values reported in the literature. Gas chromatography/mass spectrometry was used to characterize the newly synthesized products and evaluate their purity. The operating conditions were optimized using a model reaction in which the catalyst amount, temperature, time, and solvent effect were evaluated. Antibacterial activity was tested against approved Gram-positive and Gram-negative strains for previously mentioned compounds

The chemical composition, in vitro, and in silico studies of Lavandula mairei essential oil

Lavandula mairei is an aromatic, and medicinal plant endemic to Morocco, mainly found in the southeastern region of the Kingdom, and used in traditional medicine for its many benefits. The purpose of the study was to identify the chemical composition of Lavandula mairei essential oil using Gas Chromatography - Tandem Mass Spectrometry, to evaluate the antimicrobial activity of the plant against bacterial strains (Staphylococcus aureus, Staphylococcus aureus MRSA, Enterococcus faecalis, Escherichia coli ATCC 25922, Escherichia coli ESBL, Klebsiella pneumoniae ATCC 700603), and two fungal strains (Aspergillus niger ATCC 10231, Candida albicans ATCC 16404) in order to measure the microbial growth inhibition zone diameter, and to determine the minimum inhibitory, bactericidal, and fungicidal concentration of the essential oil (MIC, MBC, and MFC). Concerning antioxidant activity, six assays (6DPPH, and 1ABTS Free Radical Scavenging Assay, Total Antioxidant Capacity, Hydroxyl Radical, Reducing Power, and β-Carotene Bleaching Inhibition) were performed to determine the antioxidant potential of the essential oil. For the in silico aspect, molecular docking studies were performed to explore the potential interactions of some compounds with five microbial targets (i) Dihydropteroate synthase (1AJ0), ii) The elongation factor EF-Tu (1OB2), iii) d-alanine ligase (2I80), iv) DNA gyrase (2XCT), v) The cytochrome P450 monooxygenase (5V5Z), and 2ADMET prediction analysis was completed on a compound designated as dehydroabietinol. Carvacrol was identified as the major compound (36.38%) by analysis of the chemical composition, E. coli ATCC 25922 (MIC = 1.87 mg/mL ± 0.00, MBC = 15.00 mg/mL ± 0.00), and Enterococcus faecalis (MIC = 0.23 mg/mL ± 0.00, MBC = 5.53 mg/mL ± 2.77) were the most sensitive to the antibacterial treatment, and Candida albicans was resistant to the essential oil. The highest antioxidant potential of the plant was observed in the β-carotene bleaching inhibition test (IC50 = 1.55 mg/mL ± 0.009 and 90 % of inhibition). In the in silico study, the compound dehydroabietinol provided relevant evidence for molecular docking, and this was confirmed by the ADMET prediction analysis. The results of the study were significant, and further experiments will be necessary to find out more about the biological properties of Lavandula mairei